Symmetric Dimethylarginine is Altered in Patients After Myocardial Infarction and Predicts Adverse Outcomes.
Acute myocardial infarction (AMI) is the leading cause of morbidity and mortality worldwide. Damage to the endothelium is the earliest event in atherothrombosis, including AMI. Nitric oxide (NO), an endothelium-derived compound, protects the vasculature from damage. This study evaluated whether an association exists between plasma concentration of endogenous NO-related pathway metabolites linked to AMI and major adverse cardiovascular events (MACE) after AMI. We compared plasma concentrations of NO-related pathway metabolites in patients after AMI (n=60) and healthy controls (n=27) and investigated the prognostic value of these metabolites for post-AMI MACE development over a median of 3.5-years. In search of biomarkers, we compared plasma concentrations of dimethylarginines (ADMA, SDMA), citrulline, arginine and ornithine using ultra performance liquid chromatograph coupled with a mass spectrometer. Patients after AMI had higher concentrations of dimethylarginines, compared to controls (p=0.0068, p<0.0001, respectively). Conversely, the concentration of citrulline was lower in the AMI group (p=0.0006). The concentration of SDMA was higher in patients who developed MACE than in those who did not (p=0.015). SDMA was the only independent predictor of MACE in multivariate analysis (p=0.023). There was an intermediate, negative correlation between plasma SDMA level and platelet reactivity (r=-0.33, p=0.02). Plasma concentration of dimethylarginines differs between patients with AMI and healthy volunteers. The study's novel finding is that SDMA is an independent predictor of MACE during a 3.5 year follow-up period after AMI.


Molecular identification of Cryptosporidium spp. in seagulls, pigeons, dogs, and cats in Thailand.
Zoonotic Cryptosporidium spp., particularly C. meleagridis, C. canis, and C. felis, are enteric protozoa responsible for major public health concerns around the world. To determine the spread of this parasite in Thailand, we conducted molecular identification of Cryptosporidium spp. from animal samples around the country, by collecting and investigating the feces of seagulls (Chroicocephalus brunnicephalus and Chroicocephalus ridibundus), domestic pigeons (Columba livia domestica), dogs, and cats. Seagull and pigeon samples were collected at the seaside and on the riverside to evaluate their potential for waterborne transmission. Ten pigeon samples were combined into one set, and a total of seven sets were collected. Seventy seagull samples were combined into one set, and a total of 13 sets were collected. In addition, 111 dog samples were collected from cattle farms, and 95 dog and 80 cat samples were collected from a temple. We identified C. meleagridis in pigeons, Cryptosporidium avian genotype III in seagulls, C. canis in dogs, and C. felis in cats. In the temple, the prevalence was 2.1% (2/95) for dogs and 2.5% (2/80) for cats. No Cryptosporidium was found in dog samples from cattle farms. These are the first findings of C. meleagridis in domestic pigeons, and Cryptosporidium avian genotype III in seagulls. Our study invites further molecular epidemiological investigations of Cryptosporidium in these animals and their environment to evaluate the public health risk in Thailand.


Longitudinal study of renal prostaglandin excretion in cirrhotic rats: relationship with the renin-aldosterone system.
1. A cross-sectional study (protocol A) was performed in 19 rats with cirrhosis, induced by carbon tetrachloride (CCl4), and ascites and in 10 control animals to assess renal prostaglandin (PG) excretion in experimental cirrhosis. In an additional group of animals, including nine rats chronically exposed to CCl4 (CCl4 rats) and six control rats, a longitudinal study (protocol B) was performed to investigate the temporal relationship between changes in renal PG excretion, the renin--aldosterone system and renal function. 2. Urinary PG excretion was assessed by specific radioimmunoassay of PGE2, PGF2 alpha, 6-keto-PGF1 alpha and thromboxane (TX) B2 after extraction with octadecyl silica cartridges and h.p.l.c. purification. Recoveries for each prostanoid (61 +/- 8% for PGE2, 64 +/- 12% for PGF2 alpha, 65 +/- 11% for 6-keto-PGF1 alpha and 66 +/- 17% for TXB2) were determined in every sample by adding tritiated standards, and the final values were corrected according to the individual recoveries. 3. Cirrhotic rats with ascites in protocol A showed a significantly higher plasma renin and aldosterone concentrations and urinary excretion of 6-keto-PGF1 alpha and TXB2 than did control animals. Urinary excretion of PGE2 and PGF2 alpha, however, was significantly reduced in cirrhotic animals as compared with controls. 4. In CCl4 rats included in protocol B, there was a close chronological relationship between the activation of the renin-aldosterone system, as estimated by urinary aldosterone excretion, the onset of sodium retention and the increase in urinary excretion of 6-keto-PGF1 alpha and TXB2. The urinary excretion of PGE2 and PGF2 alpha in CCl4 rats was reduced throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)


Resurrecting an unsalvageable lower incisor with a mono-block approach.
Contemporary techniques, as well as the availability of bioactive and adhesive materials in endodontics, have helped revivifying teeth that were deemed hopeless. These newer materials and techniques would enable the clinician: (a) to predictably stop microbial activity (b) to achieve a total corono-apical fluid tight seal and (c) to strengthen mutilated teeth by obtaining intra-radicular reinforcement through mono-block effect. This case report demonstrates the successful treatment of a mutilated anterior tooth with the use of bioactive and adhesive materials to obtain a total seal and mono-block effect. This article also shows the use of a simple method in the placement of root filling cement into the root canal.


The Wolff-Parkinson-White syndrome: the cellular substrate for conduction in the accessory atrioventricular pathway.
The longstanding quest for the anatomical basis of the Wolff-Parkinson-White syndrome has left many unanswered questions. The ultrastructural morphology of the myocytes comprising accessory atrioventricular pathways, which are capable of rapid and variable conduction, is central to understanding the development and behaviour of this congenital anomaly, but remains unknown. Examination of three surgically resected pathways was performed to determine their underlying cellular morphology and the pattern of intercellular coupling, by correlative light microscopy, electron microscopy and confocal scanning laser microscopy combined with immunohistochemical localization of the cardiac gap-junctional protein, connexin43. Two left-sided pathways were composed of myocardium of 'normal working ventricular' type. The right-sided pathway was composed almost entirely of highly abnormal myocytes characterized by aberrant myofibril organisation, with a lack of A-band material and abnormal mitochondria, but normal intact intercalated disks no different from those seen in left-sided pathways. The gap junctions of all pathways were composed of connexin43 distributed as in ventricular myocardium, and not as found in atrial or atrioventricular nodal tissues. While myocytes of abnormal structure were present in one of the accessory atrioventricular pathways examined, all pathways had morphologically normal gap junctions, the structures responsible for efficient intercellular coupling, with a pattern of distribution suggestive of working ventricular myocardium.


Antimicrobial susceptibility of hazard analysis critical control point Escherichia coli isolates from federally inspected beef processing plants in Alberta, Saskatchewan, and Ontario.
A survey to estimate the prevalence of antimicrobial resistance in Escherichia coli was conducted in 7 Canadian federally inspected processing plants during 2001. Escherichia coli isolates were recovered during routine hazard analysis critical control point sampling from beef carcasses and trim and subsequently tested for their antimicrobial susceptibility by using susceptibility panels. Of the 2653 isolates analyzed, 68% were sensitive to all 18 antimicrobials tested. For 14 of the 18 antimicrobials evaluated, the percentage of resistant isolates was < or = 1. Twenty-five percent of the isolates were resistant to tetracycline, 9% to sulfamethoxazole, 7% to streptomycin, and 3% to ampicillin. Multiple resistance was found in 12% of the isolates, with 7% showing resistance to 2 antimicrobials, 2% to 3 antimicrobials, 2% to 4 antimicrobials, and 1% to 5 or more antimicrobials. Forty-five different antimicrobial resistance patterns were observed. The reasons for the development of the antimicrobial resistance were not investigated in this study. This study was useful as a pilot to help to develop a national antimicrobial resistance surveillance program in Canada. This study indicates that laboratory standardization is possible for consistent results across the country and that the indicator organism, E. coli, is fairly easy to obtain for surveillance but Salmonella are not, due to their low prevalence in beef.


Levels of the glutamic oxaloacetic transaminase of erythrocytes of pregnant women and of cord bloods of newborn infants.
The mean basal specific activity (S.A.) of the glutamic oxaloacetic transaminase of erythrocytes (EGOT) for a group of 64 pregnant women was lower (p less than 0.001) than the value for the cord bloods of newborn infants, and lower (p less than 0.001) than the value for adults who had a top limit of S.A. of EGOT. In establishing the top limit of the S.A., it is important that the mean basal S.A. of the cord bloods from 49 newborn infants was identical to the mean basal S.A. of adults who had an adequate supplement of pyridoxine. There were no differences in the mean basal S.A.'s of the cord bloods between asymptomatic mothers and mothers who had anemia, edema, hypertension, proteinuria and glucosuria. An infant may be born with a top limit of S.A. which is non-deficient in pyridoxal 5'-phosphate, but a mother can have a low level of the transaminase, and which is deficient in the coenzyme.


Tumor necrosis factor-induced interleukin-8 expression in cultured human airway epithelial cells.
The effects of tumor necrosis factor-alpha (TNF-alpha) on interleukin-8 (IL-8) expression and generation were examined in primary cultured human airway epithelial cells (HAEC) and a human lung epithelial cell line (A549). TNF-alpha increased IL-8 mRNA and protein expression in HAEC in a concentration- and time-dependent manner and these effects were inhibited by dexamethasone (1 microM). There was no change in the stability of IL-8 mRNA, and a nuclear run-on assay confirmed that TNF-alpha increased IL-8 gene transcription. TNF-alpha-induced IL-8 mRNA expression showed a biphasic response in HAEC, with an early increase at 2 h followed by a sustained increase from 8 h, which was abolished by the addition of cycloheximide, suggesting that the synthesis of another protein was involved. A549 cells also increased IL-8 secretion and mRNA after incubation of TNF-alpha, with inhibition by dexamethasone. However, A549 cells showed only an early single peak. A549 cells showed a 250-fold increase in the generation of IL-8 immunoreactivity, whereas primary cultured HAEC showed only a threefold increase, suggesting that HAEC and A549 cells may respond to TNF-alpha in different ways. The sustained increase in IL-8 secretion due to an increase in gene transcription in response to TNF-alpha may be an important amplification step in inflammatory diseases of the airways.


Parametric representation of Stiles-Crawford functions: normal variation of peak location and directionality.
Evidence suggests that the psychophysically determined Stiles-Crawford effect of the first kind (SCE) reflects waveguide properties of human photoreceptors. The peak of the SCE data set is assumed to reflect the principal alignment tendencies, and the spread (e.g., rho value, the curvature or width at half-height) is assumed to reflect the directionality (i.e., interreceptor differences in alignment) of the population of photoreceptors being tested. As such, disruption of the normal SCE can be used and/or has been used (1) to document early natural history of retinal pathology involving the photoreceptors, (2) to provide a firm rationale for therapeutic intervention, and (3) to provide a method for monitoring therapies designed to alter the natural course of retinal-disease processes. We report large-sample norms for foveal SCE peak location and spread (horizontal peak location, nasal 0.51 +/- 0.72, horizontal rho value 0.047 +/- 0.013, vertical peak location, superior 0.20 +/- 0.64, vertical rho value 0.053 +/- 0.012), compare these norms with values determined in other laboratories, and discuss the various mathematical forms used for the empirical description of SCE data sets.


p53, apoptosis and radiosensitivity--experimental and clinical data.
The tumor suppressor gene p53 is the most frequently mutated gene found in human tumors. The p53 protein is a central regulator of the cell cycle and of the induction of apoptosis after genotoxic stress, e.g. due to radiation or drugs. p53 functions mainly through transcriptional control triggered by DNA damage and influences multiple response pathways. Because of this important role in the response of cells to radiation, the interrelation between p53 status and radiosensitivity has found wide interest. Experimental and clinical data are discussed to explain the mechanism by which p53 influences the cellular response to radiation and to demonstrate the clinical relevance.


Hidden k-Space Magnetoelectric Multipoles in Nonmagnetic Ferroelectrics.
In condensed matter systems, the electronic degrees of freedom are often entangled to form complex composites, known as hidden orders, which give rise to unusual properties, while escaping detection in conventional experiments. Here we demonstrate the existence of hidden k-space magnetoelectric multipoles in nonmagnetic systems with broken space-inversion symmetry. These k-space magnetoelectric multipoles are reciprocal to the real-space charge dipoles associated with the broken inversion symmetry. Using the prototypical ferroelectric PbTiO_{3} as an example, we show that their origin is a spin asymmetry in momentum space resulting from the broken space inversion symmetry associated with the ferroelectric polarization. In PbTiO_{3}, the k-space spin asymmetry corresponds to a pure k-space magnetoelectric toroidal moment, which can be detected using magnetic Compton scattering, an established tool for probing magnetism in ferromagnets or ferrimagnets with a net spin polarization, which has not been exploited to date for nonmagnetic systems. In particular, the k-space magnetoelectric toroidal moment combined with the spin-orbit interaction manifest in an antisymmetric magnetic Compton profile that can be reversed using an electric field. Our work suggests an experimental route to directly measuring and tuning hidden k-space magnetoelectric multipoles via specially designed magnetic Compton scattering measurements.


Diagnosis and management of chronic intestinal pseudo-obstruction syndromes in infancy and childhood.
Chronic intestinal pseudo-obstruction is a rare disorder characterized by ineffective intestinal propulsion in the absence of mechanical factors. It depends on isolated or associated disturbances of intrinsic and extrinsic innervation of the smooth muscle, neurotransmitters and hormones. In children the most common causes are postoperative paralytic ileus, pneumonia or pancreatitis, occurring usually in the first year of life. There is also hereditary transmission, comprising the familial visceral myopathy (hollow visceral myopathy) and the familial visceral neuropathy. The pseudo-obstruction may be associated with congenital anomalies (digestive or not) in 10 to 30% of the cases, mainly malrotation, pyloric stenosis and bladder atony. Diagnostic difficulties may lead to exploratory laparotomy. A precise diagnosis requires judicious interpretation of radiologic, manometric, radioisotopic and hystologic findings. Medical treatment includes drugs acting on gastrointestinal motility as well as hydroelectric and nutritional support, besides treatment or prevention of infections. It is possible that in the future these patients may be treated by surgical implantation of electrodes promoting gastrointestinal myoelectrical stimulation.


Proof-of-concept: 3D bioprinting of pigmented human skin constructs.
Three-dimensional (3D) pigmented human skin constructs have been fabricated using a 3D bioprinting approach. The 3D pigmented human skin constructs are obtained from using three different types of skin cells (keratinocytes, melanocytes and fibroblasts from three different skin donors) and they exhibit similar constitutive pigmentation (pale pigmentation) as the skin donors. A two-step drop-on-demand bioprinting strategy facilitates the deposition of cell droplets to emulate the epidermal melanin units (pre-defined patterning of keratinocytes and melanocytes at the desired positions) and manipulation of the microenvironment to fabricate 3D biomimetic hierarchical porous structures found in native skin tissue. The 3D bioprinted pigmented skin constructs are compared to the pigmented skin constructs fabricated by conventional a manual-casting approach; in-depth characterization of both the 3D pigmented skin constructs has indicated that the 3D bioprinted skin constructs have a higher degree of resemblance to native skin tissue in term of the presence of well-developed stratified epidermal layers and the presence of a continuous layer of basement membrane proteins as compared to the manually-cast samples. The 3D bioprinting approach facilitates the development of 3D in vitro pigmented human skin constructs for potential toxicology testing and fundamental cell biology research.


Observations on the fetal morphology in Myocastor coypus bonariensis (coypu) (Rodentia, Myocastoridae).
The goal of this work was to characterize the morphology of fetuses of Myocastor coypus bonariensis (coypu) after 60, 90, 120 and 135 days post-coitus (d.p.c.). At all the ages, gestational sacs showed an elliptical shape. Placentas were discoidal, with a unilobular external appearance in fetuses of 60 d.p.c. and with lobulations separated by a groove in fetuses of other ages. The umbilical cord, wrapped around the fetal body, showed a proximal dilatation in 60-d.p.c. fetuses, being its course uniform and a little spiral in the other ages. The 60-d.p.c. fetuses showed differentiation of corporal regions, prominent encephalic vesicles and little developed earlobes located in the laterals of the skull, in the limit with the cervical area and in straight line with the optical vesicles. The primitive forelimbs showed differentiation of arm, forearm and hand. In the hindlimbs, the inter-digital membrane was observed joining the fingers along all their length. Fetuses of 90 d.p.c. showed developed eyelids and closed palpebral cleft, developed auricular pavilions (earlobes), hairy follicles in the facial region (vibrissae) and in the skull and bent limbs. Fetuses of 120 and 135 d.p.c. showed a bodily cover constituted by a dense pilous covering, spread palpebral clefts, open mouth, bent limbs and inter-digital membranes in the hindlimbs.


Arctic cut-off high drives the poleward shift of a new Greenland melting record.
Large-scale atmospheric circulation controls the mass and energy balance of the Greenland ice sheet through its impact on radiative budget, runoff and accumulation. Here, using reanalysis data and the outputs of a regional climate model, we show that the persistence of an exceptional atmospheric ridge, centred over the Arctic Ocean, was responsible for a poleward shift of runoff, albedo and surface temperature records over the Greenland during the summer of 2015. New records of monthly mean zonal winds at 500 hPa and of the maximum latitude of ridge peaks of the 5,700±50 m isohypse over the Arctic were associated with the formation and persistency of a cutoff high. The unprecedented (1948-2015) and sustained atmospheric conditions promoted enhanced runoff, increased the surface temperatures and decreased the albedo in northern Greenland, while inhibiting melting in the south, where new melting records were set over the past decade.


[Study on extraction technology of soyasaponins from residual of bean ware].
To find out the optimum extraction technology of soyasaponins from residual of bean ware. The optimum extraction conditions were investigated by the orthogonal design, and the content of soyasaponins was determined by UV-spectro-pho-tometry. The optimum extraction technology was A3B1C1, that is adding 7 times and 6 times amount of 70% alcohol and refluxing for two times and each time for 1.0 h. The selected technology showed higher yield of soyasaponins, good stability and high efficient.


Steric aspects of agonism and antagonism at beta-adrenoceptors: synthesis of and pharmacological experiments with the enantiomers of formoterol and their diastereomers.
The enantiomers of formoterol (R;R and S;S) and their diastereomers (R;S and S;R) were synthesized and purified using a new procedure which required the preparation of the (R;R)- and (S;S)-forms of N-(1-phenylethyl)-N-(1-(p-methoxyphenyl)-2-propyl)-amine as important intermediates. The enantiomeric purity obtained was greater than 99.3%, usually greater than 99.7%. The four stereoisomers were examined with respect to their ability to interact in vitro with beta-adrenoceptors in tissues isolated from guinea pig. The effects measured were (1) relaxation of the tracheal smooth muscle (mostly beta 2), (2) depression of subtetanic contractions of the soleus muscle (beta 2), and (3) increase in the force of the papillary muscle of the left ventricle of the heart (beta 1). All enantiomers caused a concentration-dependent and complete relaxation of the tracheal smooth muscle which was inhibited by propranolol. The order of potency was (R;R) much greater than (R;S) = (S;R) greater than (S;S). There was a 1,000-fold difference in potency between the most and the least potent isomer. The presence of the (S;S)-isomer did not affect the activity of the (R;R)-isomer on the tracheal smooth muscle. Also on the skeletal and cardiac muscles (R;R)-formoterol was more potent than its (R;S)-isomer. The selectivity for beta 2-adrenoceptors appeared to be slightly higher for the (R;R)-isomer than for the (R;S)-isomer. The potency of the (S;R)- and (S;S)-isomers on the papillary muscle was too low to be determined accurately.(ABSTRACT TRUNCATED AT 250 WORDS)


Evaluating the Patient Boarding during Omicron Surge in Hong Kong: Time Series Analysis.
The fifth wave of COVID-19 outbreaks in Hong Kong (HK) from January to March 2022 has the highest confirmed cases and deaths compared with previous waves. Severe hospital boarding (to inpatient wards) was noted in various Emergency Departments (EDs). Our objective is to identify factors associated with hospital boarding during Omicron surge in HK. We conducted a retrospective cohort study including all ED visits and inpatient (IP) ward admissions from January 1st to March 31st, 2022. Vector Autoregression model evaluated the effects of a single variable on the targeted hospital boarding variables. Admissions from elderly homes with 6 lag days held the highest positive value of statistical significance (t-stat = 2.827, P < .05) caused prolonged admission waiting time, while medical patients with 4 lag days had the highest statistical significance (t-stat = 2.530, P < .05) caused an increased number of boarding patients. Within one week after impulses, medical occupancy's influence on the waiting time varied from 0.289 on the 1st day to -0.315 on the 7th day. While occupancy of medical wards always positively affected blocked number of patients, and its response was maximized at 0.309 on the 2nd day. Number of confirmed COVID-19 cases was not the sole significant contributor, while occupancy of medical wards was still a critical factor associated with patient boarding. Increasing ward capacity and controlling occupancy were suggested during the outbreak. Moreover, streamlining elderly patients in ED could be an approach to relieve pressure on the healthcare system.


Cu2+-Modulated in situ growth of quantum dots for split-type photoelectrochemical immunoassay of prostate-specific antigen.
A split-type photoelectrochemical immunosensor was designed for the ultrasensitive monitoring of prostate-specific antigen (PSA) based on a Cu2+-mediated catalytic reaction for inhibiting the in situ generation of CdS quantum dots (QDs) coupled with the enhancement of the CdS/MoS2 heterojunction; it was constructed by the stepwise modification of MoS2 QDs and CdS QDs onto an ITO electrode surface. In the presence of PSA, CuO NP-labeled anti-PSA antibodies were immobilized onto an anti-PSA antibody-modified 96-well plate via a sandwich immunoreaction and dissolution by hydrochloric acid to obtain a large number of Cu2+ ions. As the Cu2+-triggered catalytic oxidization of glutathione occurred, the in situ growth of CdS QDs as a signal indicator was significantly suppressed, resulting in reduction in the photocurrent response. Under optimal conditions, the biosensor exhibited desirable linearity in the range from 0.5 pg mL-1 to 10 ng mL-1, low detection limit of 0.29 pg mL-1, satisfactory selectivity, and good stability. It was applied to PSA detection in human serum, suggesting a great potential for early diagnostics of some cancers.


Lisfranc's tarsometatarsal fracture-dislocation.
Lisfranc's fracture-dislocation is an injury at the tarsometatarsal joints. Usually the metatarsals dislocate dorsally and laterally. These frectures can be subtle, and a knowledge of the normal relationships is essential. Review of foot radiographs indicated that the most constant normal relationship of the tarsometatarsal joints is the alignment of the second tarsometatarsal joint, which, fortunately, is involved in most Lisfranc's dislocations. There is more variation in normal alignment of the other tarsometatarsal joints, but gross abnormalities are detectable, and the presence of associated chip fractures and clinical correlation will usually clarify more subtle cases.


Novel Alternating Current Electrospinning of Hydroxypropylmethylcellulose Acetate Succinate (HPMCAS) Nanofibers for Dissolution Enhancement: The Importance of Solution Conductivity.
Novel, high-yield alternating current electrospinning (ACES) and direct current electrospinning methods were investigated to prepare high-quality hydroxypropylmethylcellulose acetate succinate (HPMCAS) fibers for the dissolution enhancement of poorly soluble spironolactone. Although HPMCAS is of great pharmaceutical importance as a carrier of marketed solid dispersion-based products, it was found to be unprocessable using electrospinning. Addition of small amounts of polyethylene oxide as aid polymer provided smooth fibers with direct current electrospinning but strongly beaded products with ACES. Solution characteristics were thus modified by introducing further excipients. In the presence of sodium dodecyl sulfate, high-quality, HPMCAS-based fibers were obtained even at higher throughput rates of ACES owing to the change in conductivity (rather than surface tension). Replacement of sodium dodecyl sulfate with non-surface-active salts (calcium chloride and ammonium acetate) maintained the fine quality of nanofibers, confirming the importance of conductivity in ACES process. The HPMCAS-based fibers contained spironolactone in an amorphous form according to differential scanning calorimetry and X-ray powder diffraction. In vitro dissolution tests revealed fast drug release rates depending on the salt used to adjust conductivity. The presented results signify that ACES can be a prospective process for high-scale production of fibrous solid dispersions in which conductivity of solution has a fundamental role.


[Dependence of normal tail regeneration in Xenopus larvae upon a diencephalic factor in the central canal].
Tail regeneration inXenopus larvae is substantially reduced and morphologically disturbed if the continuity of the neural tube at the base of the tail is permanently impaired. This operation is believed to block the transport of a growth factor derived from the diencephalic roof and transmitted to the regeneration site via the central canal. The following experimental data support this hypothesis: 1. Tails transplanted into host larvae and partially amputated after revascularisation but without connection between the transplant and the host neural tube regenerate in the same abnormal manner as do tails in larvae without a continuous neural tube. 2. Simple transsection of the neural tube followed by reunion of the separated parts allows of normal regeneration of the tail provided the patency of the central canal is restored. 3. Occlusion of the ventricles of the brain by injection of agar does not affect normal tail motility but causes the same atypical tail regeneration as does discontinuity of the neural tube. 4. Coagulation of the telencephalon and major parts of the mesencephalic roof leaves tail regeneration unimpaired provided the operation did not lead to an obstruction behind the third ventricle; destruction of the diencephalon has the same effect on regeneration as severance of the neural tube. This effect may still be observed if only a very small part of the diencephalic roof containing the subcommissural organ is coagulated. 5. According to literature the subcommissural organ gives rise to the Reissner's fibre which passes the whole length of the central canal and releases its secretion through the wall of the terminal vesicle into the surrounding tissues. Therefore the subcommissural organ might well be the source of the postulated factor promoting tail regeneration.


Intravenous Immunoglobulin as an Immunomodulating Agent in Antineutrophil Cytoplasmic Antibody-Associated Vasculitides: A French Nationwide Study of Ninety-Two Patients.
Intravenous immunoglobulin (IVIG) represents a therapeutic alternative in antineutrophil cytoplasmic antibody-associated vasculitides (AAV), but its efficacy has been evaluated in only 2 small prospective trials. The aim of this study was to evaluate the efficacy and safety of IVIG in patients with AAV. We conducted a nationwide retrospective study of patients who received IVIG as immunomodulatory therapy for AAV. A total of 92 patients (mean age 51 years) presenting with either granulomatosis with polyangiitis (Wegener's) (68%), eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (22%), or microscopic polyangiitis (10%) received at least 1 course of IVIG. Antineutrophil cytoplasmic antibodies were present in 72% during the flare that required IVIG, as determined by immunofluorescence assay. IVIG was initiated because of relapsing disease in 83% of cases. IVIG was given for a median of 6 months (range 1-156 months) and in combination with corticosteroids in 21% of the patients or with other immunosuppressive agents in 77%. Efficacy of IVIG was assessed in the entire population and in a subset of 34 patients with unmodified background therapy. Remission rates at 6 months were 56% in the entire population and 58% in the unmodified background therapy group. Refractory disease and treatment failure at 6 months were observed in 7% and 18% in the whole population and 3% and 21% in the unmodified background therapy group, respectively. Adverse events (AEs) occurred in 33%, including serious AEs in 12% and AEs leading to discontinuation of IVIG in 7%. This large study shows the clinical benefit of IVIG as adjunctive therapy, with an acceptable tolerance profile, and thus supports its use in AAV patients with refractory or relapsing disease.


Formation of methyl radicals from decomposition of methyl-substituted silanes over tungsten and tantalum filament surfaces.
The formation of methyl radical from the decomposition of four methyl-substituted silane molecules, including monomethylsilane (MMS), dimethylsilane (DMS), trimethylsilane (TriMS), and tetramethylsilane (TMS), over tungsten and tantalum filament surfaces has been systematically studied using vacuum ultraviolet laser ionization mass spectrometry. The methyl radical intensity increases with temperature for both filaments in the low-temperature region; however, beyond the optimum temperature, a gradual decrease in the methyl intensity was observed for MMS, DMS, and TriMS when using Ta, whereas the intensity reaches a plateau with W. This is due to the fact that Ta is more efficient in releasing surface-bound H and forming active sites, leading to the adsorption of methyl radicals on the metal surface in the high-temperature regions. The apparent activation energy for methyl radical formation from the dissociation of MMS, DMS, TriMS, and TMS molecules on both W and Ta filaments increases with the increasing number of methyl substitution. The dissociation process is believed to be initiated by the Si-H bond cleavage and followed by Si-CH3 bond breaking. The obtained low activation energy values for methyl radical formation in the range of 51.1-84.7 kJ·mol(-1) suggest that the ejection of CH3 radicals is accompanied by the formation of a Si moiety bound to the metal surface. Overall, TMS produces the least number of methyl radicals on both filaments with the highest activation energy. The numbers of methyl radicals produced when using MMS, DMS, and TriMS are similar, but MMS gives the lowest activation energy.


[Ester prodrug of scutellarin: synthesis, physicochemical property and degradation].
To establish the fundamentals for the design of scutellarin prodrug and formulation with feasible physicochemical and biopharmaceutical properties by esterifying scutellarin, an active component with poor absorption extracted from Erigeron breviscapus of Chinese medicine. With the method of salifying followed by esterifying, ethyl and benzyl ester of scutellarin were synthesized. Glycolamide ester of scutellarin was also synthesized with an improved method. Their structures were confirmed by MS and 1H NMR. The solubility and partition coefficient of the prodrugs were determined and their degradations were investigated in various buffers and in human plasma. The emulsion and cyclodextrin complex of glycolamide ester were prepared and the protection of the ester from degradation was compared in the intestinal tract contents. Furthermore, the degradation of glycolamide ester in the homogenates of various intestinal segments was studied. Results Three prodrugs were synthesized successfully and their structures were confirmed. Glycolamide ester of scutellarin showed better stability in the aqueous solution (t(1/2) approximately =16 d, pH 4.2) and the shortest half-life in the human serum (t(1/2) approximately =7 min). Compared with scutellarin, the solubility of glycolamide ester was increased about ten times in pH 4.0 buffer, and about thirty five times in water. Partition coefficient of the glycolamide ester increased significantly from -2.56 to 1.48. However, the ester degradation in the homogenates of intestinal mucus would be an obstacle for its absorption. The degradation rates were in the order duodenum > ileum > or = jejunum > colon. The emulsion showed a better protection of glycolamide ester from the degradation than cyclodextrin complex. Glycolamide ester of scutellarin shows better physicochemical properties than ethyl and benzyl eater of scutellarin, but its stability in intestinal tract needs to be improved. The emulsion or / and colon-targeted delivery may be selected as one of strategies to decrease the presystemic degradation.


Skeletal Rearrangement of Twisted Polycyclic Aromatic Hydrocarbons under Scholl Reaction Conditions.
Treatment of a twisted polycyclic aromatic hydrocarbon containing cyclooctatetraene fused by two 9,9'-bifluorenylidene units under the Scholl reaction conditions (FeCl3 or 2,3-dichloro-5,6-dicyano-1,4-benzoquinone and scandium trifluoromethanesulfonate) led to stepwise skeletal rearrangements to afford initially a hydrocarbon with a seven-membered ring and then tetrabenzo[a,d,j,m]coronene with all six-membered rings. The course of the rearrangement was interpreted in terms of the acid-catalyzed isomerization of 9,9'-bifluorenylidene into dibenzo[g,p]chrysene moieties on the basis of theoretical investigations.


Pyloric stenosis a 100 years after Ramstedt.
Conrad Ramstedt performed the first pyloromyotomy for what is now called idiopathic hypertrophic pyloric stenosis 100 years ago. The intervening century has seen the management of this condition transformed but the underlying cause remains a mystery. This article reviews the treatment of this condition before and after the introduction of pyloromyotomy and the advances made subsequently towards understanding its cause.


[About the heterogeneity in adolescents with gender identity disorder: differential importance of psychiatric comorbidity and considerations of individual psychodynamics].
Gender identity disorder (GID), gender dysphoria (GD) respectively, is considered a multifactorial disease whose etiology is subject to complex bio-psycho-social conditions, each with different weighting. As a result, therapists, who treat children and adolescents with GID/GD, have to deal with a very heterogeneous group with individually varying causes, differing psychopathology and varying disease progression. In addition to general psychiatric aspects of development, particularly psychiatric comorbidity, but also the different individual psychodynamics--i. e. the specific constellation of conflicts and possible ego deficits and structural deficits in the learning history of the person are of differential importance. In regard to the indication for gender reassignment measures this sometimes is relevant for the decision. The difficulties arising for decision making and the usefulness of a systematic evaluation of case reports as a basis for further optimization of the treatment recommendations are illustrated by two case reports. In the course of this, also the disadvantages and potential dangers of too early diagnostic definition and introduction of gender somato-medical and legal measures are shown exemplarily.


Insights into the structural determinants of substrate specificity and activity in mouse aldehyde oxidases.
In this work, a combination of homology modeling and molecular dynamics (MD) simulations was used to investigate the factors that modulate substrate specificity and activity of the mouse AOX isoforms: mAOX1, mAOX2 (previously mAOX3l1), mAOX3 and mAOX4. The results indicate that the AOX isoform structures are highly preserved and even more conserved than the corresponding amino acid sequences. The only differences are at the protein surface and substrate-binding site region. The substrate-binding site of all isoforms consists of two regions: the active site, which is highly conserved among all isoforms, and a isoform-specific region located above. We predict that mAOX1 accepts a broader range of substrates of different shape, size and nature relative to the other isoforms. In contrast, mAOX4 appears to accept a more restricted range of substrates. Its narrow and hydrophobic binding site indicates that it only accepts small hydrophobic substrates. Although mAOX2 and mAOX3 are very similar to each other, we propose the following pairs of overlapping substrate specificities: mAOX2/mAOX4 and mAOX3/mAXO1. Based on these considerations, we propose that the catalytic activity between all isoforms should be similar but the differences observed in the binding site might influence the substrate specificity of each enzyme. These results also suggest that the presence of several AOX isoforms in mouse allows them to oxidize more efficiently a wider range of substrates. This contrasts with the same or other organisms that only express one isoform and are less efficient or incapable of oxidizing the same type of substrates.


Vitamin D's Effect on Immune Function.
Ever since its discovery by Windhaus, the importance of the active metabolite of vitamin D (1,25-dihydroxyvitamin D3; 1,25-(OH)2D3) has been ever expanding. In this review, the attention is shifted towards the importance of the extra-skeletal effects of vitamin D, with special emphasis on the immune system. The first hint of the significant role of vitamin D on the immune system was made by the discovery of the presence of the vitamin D receptor on almost all cells of the immune system. In vitro, the overwhelming effect of supra-physiological doses of vitamin D on the individual components of the immune system is very clear. Despite these promising pre-clinical results, the translation of the in vitro observations to solid clinical effects has mostly failed. Nevertheless, the evidence of a link between vitamin D deficiency and adverse outcomes is overwhelming and clearly points towards avoidance of vitamin D deficiency especially in early life.


Interactions between Borrelia burgdorferi and eukaryote cells: comparative ultrastructural aspects.
In the present study, mammalian VERO cells, human polymorphonuclear leukocytes (PMN) and mouse peritoneal macrophages (MPM) were coincubated with B31 Borrelia burgdorferi strain (Bb) and examined by transmission electron microscopy. The results indicate that the spirochete adheres to the mammalian cells mainly by the apical pole and less frequently by the lateral wall. In VERO cells and MPM cell penetration is accomplished especially by cytoplasmic membrane destruction, the spirochete appearing free in the cytoplasm, but also by phagocytosis. In this latter case the pathogen is seen in phagosome. In PMN the internalization takes place exclusively by phagocytosis, the spirochete undergoing destruction in phagosomes. Sometimes an alteration of the phagosomal membrane is observable, probably produced by the pathogen as a mechanism to avoid fusion with the lysosome. Other aspects indicate the contribution of the parasitized cell cytoskeleton to the spreading of Borrelia to adjacent cells. MPM does not represent a very efficient barrier against Bb, as can be seen from the cellular behaviour of the spirochetes in this study, PMN seems to a more efficient barrier, by its unique capacity to destroy the microorganism after phagocytosis.


Construct Validity of an Instrument for Assessment of Reflective Writing-Based Portfolios of Medical Students.
Assessment of reflective writing for medical students is challenging, and there is lack of an available instrument with good psychometric properties. The authors developed a new instrument for assessment of reflective writing-based portfolios and examined the construct validity of this instrument. After an extensive literature review and pilot testing of the instrument, two raters assessed the reflective writing-based portfolios from years 2 and 3 medical students (n=135) on three occasions. The instrument consists of three criteria: organization, description of an experience and reflection on the experience. We calculated the reliability of scores using generalizability theory with a fully crossed design and two facets (raters and occasions). In addition, we measured criterion validity by testing correlations with students' scores using other assessment methods. The dependability (Φ) coefficient of the portfolio scores was 0.75 using two raters on three occasions. Students' portfolio scores represented 46.6% of the total variance across all score comparisons. The variance due to occasions was negligible, while the student-occasion interaction was small. The variance due to student-rater interaction represented 17.7%, and the remaining 27.7% of the variance was due to unexplained sources of error. The decision (D) study suggested that an acceptable dependability (Φ = 0.70 and 0.72) can be achieved by using two raters for one and two occasions, respectively. Finally, we found moderate to large effect-size correlations between students' scores in reflective writing-based portfolios and communication skills (r = 0.47) and PBL tutorials (r = 0.50). We demonstrated the presence of different sources of evidence that support construct validity of the study instrument. Further studies are warranted before utilizing this instrument for summative assessment of students' reflective writing-based portfolios in other medical schools.


Paroxysmal dystonia as the initial manifestation of multiple sclerosis.
Paroxysmal dystonia was the initial manifestation of multiple sclerosis (MS) in eight patients. The disorder was generally characterized by dystonic posturing of unilateral extremities, averaging less than one minute in duration. Facial grimacing and dysarthria occurred in two of the eight patients. This paroxysmal phenomenon was frequently the cause of diagnostic confusion. The time elapsing before other neurological symptoms of MS developed was as long as ten years.


Bridging the future of cardiac stimulation: physiologic or leadless pacing?
Cardiac simulation has moved from early life-saving pacemakers meant only to prevent asystole to current devices capable of physiologic stimulation for the treatment of heart rhythm and heart failure, that are also intended for remote patient and disease-progression monitoring. The actual vision of contemporary pacing aims to correct the electrophysiologic roots of mechanical inefficiency regardless of underlying structural heart diseases. The awareness of the residual cardiac dyssynchrony related to customary cardiac pacing has changed the concept of what truly represents "physiologic pacing". On a different perspective, leadless stimulation to abolish CIED surgery and prevent lead-related complications is becoming a priority both for young device recipients and for frail, elderly patients. Careful clinical evaluation attempts to bridge decision-making to patient-tailored therapy.


Nutritional aspects of leukocytic cytokines.
Immune responses result in a variety of metabolic adjustments that are mediated by cytokines of leukocytic origin. Of the dozens of cytokines released during an immune response, interleukin-1 (IL-1), tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) are the major mediators of intermediary metabolism. These three cytokines act in concert to decrease food intake, increase resting energy expenditure, gluconeogenesis, glucose oxidation, and hepatic synthesis of fatty acids and acute phase proteins, decrease fatty acid uptake by adipocytes and alter the distribution of zinc, iron and copper. Most of these activities result from direct interactions between the cytokine and the responding cells. IL-1, TNF alpha and IL-6 also affect changes in metabolism by changing levels of circulating insulin, glucagon and corticosterone. The nutritional impact of these metabolic changes is dependent upon age. In growing animals, increases in energy expenditure and oxidation of amino acids are balanced by lower needs associated with growth. In adult animals, energy and amino acid requirements are increased by an amount similar to the increased basal metabolic rate and amino acid oxidation. Nutrition also influences the release of cytokines and consequently affects regulation of the immune response. For example, protein deficiency results in decreased IL-1 release and impaired tissue responses to IL-1.


STABILIZING SELECTION DETECTED FOR BRISTLE NUMBER IN DROSOPHILA MELANOGASTER.
Stabilizing selection, which favors intermediate phenotypes, is frequently invoked as the selective force maintaining a population's status quo. Two main alternative reasons for stabilizing selection on a quantitative trait are possible: (1) intermediate trait values can be favored through the causal effect of the trait on fitness (direct stabilizing selection); or (2) through a pleiotropic, deleterious side effect on fitness of mutants affecting the trait (apparent stabilizing selection). Up to now, these alternatives have never been experimentally disentangled. Here we measure fitness as a function of the number of abdominal bristles within four Drosophila melanogaster lines, one with high, one with low, and two with intermediate average bristle number. The four were inbred nonsegregating lines, so that apparent selection due to pleiotropy is not possible. Individual fitness significantly increased (decreased) with bristles number in the low (high) line. No significant fitness-trait association was detected within each intermediate line. These results reveal substantial direct stabilizing selection on the trait.


Nuclear redirection of a cytoplasmic helix-loop-helix protein via heterodimerization with a nuclear localizing partner.
The DNA-binding basic domain of helix-loop-helix transcriptional (HLH) factors in several instances also serves as a nuclear localization signal (NLS). Interestingly, some members of the HLH family of proteins lack a basic domain or any other recognizable NLS and yet still display efficient nuclear localization. To study this apparent paradox, we used the hematopoietic HLH protein SCL/tal as a model. Deletion of the basic domain converted SCL/tal from nuclear to a cytoplasmic protein. However, the basic domain deficient SCL/tal protein could be redirected to the nucleus by coexpression of E2-5, an SCL/tal-binding HLH protein with an intact basic domain. These results indicate that heterodimerization of HLH proteins may take place in the cytoplasm prior to nuclear localization and that nuclear localization for HLH complexes is a dominant process requiring only a single NLS per complex.


[Rare cases of intussusceptions in children].
Intussusception is common in children under two years of age. Most of them are idiopathic whereas intussusceptions secondary to focal pathologies are rare. We report of two unusual cases of ileocolic intussusception. In one child a mobile cecum was seen, in the second child a duplication cyst of the ileocecal valve.


Culturally congruent end-of-life care for Jewish patients and their families.
This qualitative study was conducted to determine cultural influences in end-of-life care among Jewish people. The conceptual framework for this study was drawn from Leininger's culture care theory. Informants consisted of 16 professional caregivers, family members, and rabbis who had experience with end-of-life care for Jewish patients. Interviews using open-ended and focused questions were used to gather informants' descriptions of their generic values, beliefs, and practices. Findings revealed the strong influence of religious, cultural, and historical factors in caring. Sanctity of life and life promotion are central to Judaism. Caring is a communal obligation that unites the family and community into a cohesive unit. Attitudes toward death are influenced by beliefs about afterlife and suffering. The value put on expert knowledge influences patients' and family members' expectations of professional caregivers. Similarities and differences were noted among different groups of informants.


Current expert opinion and attitudes to optimize telemedicine and achieve control in patients with asthma in post-pandemic era: The COMETA consensus.
To collect perspectives and explore consensus for expert recommendations related to asthma control and the use of telemedicine among professionals who manage patients with asthma. A Delphi-like questionnaire was designed to analyse the level of agreement about several recommendations formulated by an expert scientific committee about asthma control and the use of telemedicine with this purpose. A dedicated scientific committee validated the questionnaire, which included questions about the participants' profile and the use of technological tools at a personal level or in clinical practice. The experts expressed their agreement with a Likert-scale of 9 values: 1-3 was considered no agreement, 4-6 neutral, and 7-9 agreement. A rate ≥70% with the same answer was considered consensus. SITE: The questionnaire was programmed and distributed as an internet-based survey. A pre-selected sample of 75 experts with experience in telemedicine (pulmonology, allergology, family medicine, nursing and community pharmacy) responded to a Delphi-like questionnaire composed by six questions and 52 items. Consultation was performed in two consecutive waves: the first wave was carried out from 12th of July to 8th of September of 2021; the second wave, from 25th of October to 12th of November of 2021. Three questions about asthma control (actions for achieving or maintaining control of asthma at every visit, current problems that affect asthma control, and potential solutions to offset such problems), and three questions about the impact of telemedicine in asthma control (potential benefits of telemedicine, and potential reticence about telemedicine among both patients and healthcare professionals) were included. From the 52 items inquired, 35 were agreed by consensus. The actions for achieving or maintaining control of asthma, the problems that affect asthma control, and their potential solutions were agreed by consensus. The potential benefits of telemedicine were validated by consensus. None of the potential reservations of patients about telemedicine were validated, while five out of 14 potential reservations of healthcare professionals were agreed by consensus. The COMETA consensus provides a current picture of the main problems for achieving asthma control, the benefits and the reservations about the use of telemedicine in the Spanish setting, and offers solutions. A wide interest in implementing telemedicine has been observed, although current limitations need to be overcome.


Sustainability of community-capacity to promote safer motherhood in northwestern Tanzania: what remains?
To examine the remains of the Community-Based Reproductive Health Project (CBRHP) implemented by CARE-Tanzania to address high maternal mortality in two rural districts. In early 2007, data were collected from 29 villages and used to assess sustainability of emergency transport systems, retention of village health workers (VHWs), and their potential impact on maternal health. Surveillance data from the Ministry of Health were reviewed to assess changes in prenatal and service use indicators. From 2001 through 2006, the CBRHP-trained VHWs have continued to provide education and referrals to women in their communities including prenatal and emergency obstetric care; six villages with emergency transport systems have continued for more than 5 years providing free or low-cost transport to health facilities. Selected maternal and infant health indicators, such as early prenatal care, identification of pregnancy-related danger signs, and data on maternal and infant outcomes, improved in the two targeted districts over time. The two components of CBRHP, work of VHWs and community-financing for emergency transport systems in six villages, have continued. Both of these promote maternal health and linkages with the health delivery systems. Surveillance data show changes in maternal health indicators that were targeted by the district-wide CBRHP interventions. Programs such as CBRHP, with focus on capacity-building and empowerment, can assist in mobilizing the formal and informal systems in communities, components of which may be sustained over time.


Endocarditis caused by Staphylococcus lugdunensis.
We describe a case of native valve endocarditis caused by Staphylococcus lugdunensis, a perineal skin commensal, and review 28 other cases from the medical literature. Correctly identifying this coagulase-negative organism is critical because endocarditis is usually associated with left sided valvular disruption and life-threatening embolic complications, reminiscent of disease caused by Staphylococcus aureus. Urgent surgical intervention is necessary in most cases.


Visuospatial functions in patients with spasmodic torticollis.
Visuospatial functions were studied in 18 patients with spasmodic torticollis and 18 matched controls. Subjects were examined with respect to their judgement of the subjective vertical, personal and extrapersonal orientation, the discrimination of left and right, the ability to judge angles and distances, and a drawing task. Patients showed marked deficits in extrapersonal orientation and atypical displacement errors to the right when requested to set the subjective vertical. Results were largely independent of the clinical characteristics of the disease. The pattern of results was attributed to a subtle attention deficit underlying complex measures of visuospatial functions. This may reflect a discrete dysfunction of the striatal-frontal circuits at least in a subgroup of patients.


Evaluation of urine ELISA test for detecting Helicobacter pylori infection in Taiwan: a prospective study.
To evaluate the diagnostic accuracy and clinical utility of a new ELISA (URINELISA) test for detecting Helicobacter pylori (H pylori) antibody in the urine of Taiwanese population. In this prospective study, 317 consecutive dyspeptic patients (171 men, 146 women; mean age, 51.0 years) were included. They underwent gastroendoscopy for evaluation. Invasive tests, including culture, histology, and rapid urease test (RUT), and non-invasive (13)C-urea breath test were preformed. At the same time, urine specimens were collected for URINELISA. The status of H pylori infection was considered as positive when either culture was positive, or when two of the other, RUT, histology or 13C-UBT, were positive. The sensitivity, specificity, positive predictive value, and negative predictive value of URINELISA are 91.7% (211/230), 90.8% (79/87), 96.3% (211/219), and 80.6% (79/98) respectively. This URINELISA test is reliable, inexpensive and easy-to-use. The high diagnostic accuracy warrants the use of URINELISA as a first-line screening tool for diagnosis of H pylori infection in untreated patients.


Extinction-to-backscatter ratio of Asian dust observed with high-spectral-resolution lidar and Raman lidar.
Extinction-to-backscatter ratio or lidar ratio is a key parameter in the issue of backscatter-lidar inversions. The lidar ratio of Asian dust was observed with a high-spectral-resolution lidar and a combined Raman elastic-backscatter lidar during the springs of 1998 and 1999. The measured values range from 42 to55 sr in most cases, with a mean of 51 sr. These values are significantly larger than those predicted by the Mie computations that incorporate measured Asian dust size distributions and a range of refractive index with a typical value of 1.55-0.005i. The enhancement of lidar ratio is mostly due to the nonsphericity of dust particles, as indicated by the T-matrix calculations for spheroid particles and a number of other theoretical studies. In addition, possible contamination of urban aerosols may also contribute somewhat in optically thin cases. Mie theory, although it can well describe spherical particle scattering, will not be sufficient to represent the scattering characteristics of irregular particles such as Asian dust, especially in directions larger than approximately 90 degrees when the size parameter is large.


Short-Term Effects of Thoracic Spine Manipulation on the Biomechanical Organisation of Gait Initiation: A Randomized Pilot Study.
Speed performance during gait initiation is known to be dependent on the capacity of the central nervous system to generate efficient anticipatory postural adjustments (APA). According to the posturo-kinetic capacity (PKC) concept, any factor enhancing postural chain mobility and especially spine mobility, may facilitate the development of APA and thus speed performance. "Spinal Manipulative Therapy High-Velocity, Low-Amplitude" (SMT-HVLA) is a healing technique applied to the spine which is routinely used by healthcare practitioners to improve spine mobility. As such, it may have a positive effect on the PKC and therefore facilitate gait initiation. The present study aimed to investigate the short-term effect of thoracic SMT-HVLA on spine mobility, APA and speed performance during gait initiation. Healthy young adults (n = 22) performed a series of gait initiation trials on a force plate before ("pre-manipulation" condition) and after ("post-manipulation" condition) a sham manipulation or an HVLA manipulation applied to the ninth thoracic vertebrae (T9). Participants were randomly assigned to the sham (n = 11) or the HVLA group (n = 11).The spine range of motion (ROM) was assessed in each participant immediately after the sham or HVLA manipulations using inclinometers. The results showed that the maximal thoracic flexion increased in the HVLA group after the manipulation, which was not the case in the sham group. In the HVLA group, results further showed that each of the following gait initiation variables reached a significantly lower mean value in the post-manipulation condition as compared to the pre-manipulation condition: APA duration, peak of anticipatory backward center of pressure displacement, center of gravity velocity at foot-off, mechanical efficiency of APA, peak of center of gravity velocity and step length. In contrast, for the sham group, results showed that none of the gait initiation variables significantly differed between the pre- and post-manipulation conditions. It is concluded that HVLA manipulation applied to T9 has an immediate beneficial effect on spine mobility but a detrimental effect on APA development and speed performance during gait initiation. We suggest that a neural effect induced by SMT-HVLA, possibly mediated by a transient alteration in the early sensory-motor integration, might have masked the potential mechanical benefits associated with increased spine mobility.


Defective dissociation of a "slow" RecA mutant protein imparts an Escherichia coli growth defect.
The RecA and some related proteins possess a simple motif, called (KR)X(KR), that (in RecA) consists of two lysine residues at positions 248 and 250 at the subunit-subunit interface. This study and previous work implicate this RecA motif in the following: (a) catalyzing ATP hydrolysis in trans,(b) coordinating the ATP hydrolytic cycles of adjacent subunits, (c) governing the rate of ATP hydrolysis, and (d) coupling the ATP hydrolysis to work (in this case DNA strand exchange). The conservative K250R mutation leaves RecA nucleoprotein filament formation largely intact. However, ATP hydrolysis is slowed to less than 15% of the wild-type rate. DNA strand exchange is also slowed commensurate with the rate of ATP hydrolysis. The results reinforce the idea of a tight coupling between ATP hydrolysis and DNA strand exchange. When a plasmid-borne RecA K250R protein is expressed in a cell otherwise lacking RecA protein, the growth of the cells is severely curtailed. The slow growth defect is alleviated in cells lacking RecFOR function, suggesting that the defect reflects loading of RecA at stalled replication forks. Suppressors occur as recA gene alterations, and their properties indicate that limited dissociation by RecA K250R confers the slow growth phenotype. Overall, the results suggest that recombinational DNA repair is a common occurrence in cells. RecA protein plays a sufficiently intimate role in the bacterial cell cycle that its properties can limit the growth rate of a bacterial culture.


Growth and maturation of mandibular bone in otherwise totally immobilized rhesus monkeys.
The effects of 14 days of total postcranial body immobilization (in plaster casts) on the mineralization rate and on the maturation of matrix and mineral moieties in the rhesus jaw were studied by tetracycline labeling and by density gradient methods, respectively. Immobilization did not alter the rates of periosteal and endosteal mineralization in the dense cortical bone from the lingular region of the jaw, but it did impair mineralization in osteonal bone. Osteons that continued to show radial closure did so at a normal rate. In the more trabecular cortex (premolar region) in young monkeys (3-6 kg body weight), immobilization impaired bone mineralization, as shown by lower ratios of calcium and inorganic phosphorus to hydroxyproline (Ca/HO-Pr;Pi/HO-Pr), and it reduced the rate at which the newly formed bone and mineral moieties matured. In older monkeys (6-10 kg body weight) immobilization did not alter Ca/HO-Pr and Pi/HO-Pr ratios or impair tissue maturation. These changes tended to normalize within 7 to 14 days after decasting.


IFN-alpha2b monotherapy in patients with chronic hepatitis C and persistently normal or near normal aminotransferase activity: a randomized, controlled study.
To determine the effect of interferon-alpha2b (IFN-alpha2b) on the long-term suppression of hepatitis C virus (HCV) RNA in patients with persistently normal or near normal alanine aminotransferase (ALT) activity, 76 previously untreated patients with serum HCV RNA and ALT levels <1.5 times the upper limit of normal (ULN) were randomized to receive either interferon-alpha2b (IFN-alpha2b) 5 MU three times a week for 24 weeks (n = 37) or no treatment (n = 39). HCV RNA testing was performed at the end of treatment and after a 6-month follow-up period. Intention-to-treat analysis showed that HCV RNA was detected significantly less frequently in treated than in untreated patients, at the end of both treatment and follow-up (43.2% vs. 7.7%, p < 0.001, and 21.6% vs. 5.1%, p = 0.033, respectively). Among treated patients, sustained virologic response was significantly higher in non-1 than in genotype 1 patients (8 of 26 or 30.8% vs. 0 of 11, p = 0.038). According to multiple logistic regression, untreated patients had a 13.5 times greater risk to be HCV RNA-positive compared with treated patients (p = 0.040). ALT levels flared up in 3 treated and 9 untreated patients (p = 0.07), suggesting that these flare-ups are related to the natural course of chronic HCV infection rather than to IFN-alpha2b. Thus, such patients could benefit from an IFN-alpha2b in combination with ribavirin regimen.


Investigation of the Maillard Reaction between Polysaccharides and Proteins from Longan Pulp and the Improvement in Activities.
The purpose of this study was to investigate the Maillard reaction between polysaccharides and proteins from longan pulp and the effects of reaction on their in vitro activities. The polysaccharide-protein mixtures of fresh longan pulp (LPPMs) were co-prepared by an alkali extraction-acid precipitation method. They were then dry-heated under controlled conditions for monitoring the characterization of the Maillard reaction by the measurement of the free amino group content, ultraviolet-visible spectrum, Fourier transform infrared spectrum and molecular weight distribution. All the physicochemical analyses indicated the development of the Maillard reaction between polysaccharides and proteins. The in vitro activity evaluation indicated that the Maillard reaction could effectively enhance the antioxidant, antitumor and immunostimulating activities of LPPMs. The enhancement of 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity and ferric reducing antioxidant power displayed both a positive correlation with the reaction time (p < 0.05). LPPMs dry-heated for three days obtained relatively strong inhibitory activity against HepG2 cells and SGC7901 cells, as well as strong immunostimulating effects on the nitric oxide production and tumor necrosis factor α secretion of macrophages. Maillard-type intermacromolecular interaction is suggested to be an effective and controllable method for improving the functional activities of polysaccharides and proteins from longan pulp.


Products of in vitro cleavage and polyadenylation of simian virus 40 late pre-mRNAs.
Formation of mRNA 3' termini involves cleavage of an mRNA precursor and polyadenylation of the newly formed end. Cleavage of simian virus 40 late pre-mRNA in a crude nuclear extract generated two RNAs, 5' and 3' half-molecules. These RNAs were unmodified and linear. The 5' half-molecule contained sequences upstream but not downstream of the poly(A) site and ended in a 3'-terminal hydroxyl. The 3' half-molecules comprised a family of RNAs, each of which contains only sequences downstream of the poly(A) site, and ends in a 5'-terminal phosphate. These RNAs differed only in the locations of their 5' terminus. The 3' terminus of the 5' half-molecule was the adenosine 10 nucleotides downstream of AAUAAA, at the +1 position. The 5' terminus of the longest 3' half-molecule was at +2. Thus, these two RNAs contain every nucleoside and phosphate of the precursor. The existence of these half-molecules demonstrates that endonucleolytic cleavage occurs near the poly(A) site. 5' half-molecules generated in the presence of EDTA (which blocks polyadenylation, but not cleavage) ended at the adenosine at position +1 of the precursor. When incubated in the extract under suitable conditions, they became polyadenylated. 5' half-molecules formed in 3'-dATP-containing reactions contained a single 3'-deoxyadenosine (cordycepin) residue added onto the +1 adenosine and were poor polyadenylation substrates. We infer that the +1 adenosine of the precursor becomes the first A of the poly(A) tract and provides a 3' hydroxyl group to which poly(A) is added posttranscriptionally.


Characterization of cytochrome P4502E1 turnover in transfected HepG2 cells expressing human CYP2E1.
The aim of the present study was to characterize human CYP2E1 turnover and examine the possible proteolytic pathways responsible for the rapid degradation of CYP2E1 in a transfected HepG2 cell line expressing human CYP2E1. Two methods were used to study the CYP2E1 turnover; after addition of cycloheximide, the half-life of the CYP2E1 in the intact cells was about 6 h as detected by PNP catalytic activity assay and immunoblot analysis of apoprotein content. CYP2E1 substrates or ligands such as 4-methylpyrazole, ethanol, glycerol, and dimethyl sulfoxide protected CYP2E1 against this rapid degradation, whereas CCl4 accelerated this process. The second procedure involved pulse-chase experiments after labeling CYP2E1 with [35S]methionine and immunoprecipitation with anti-human CYP2E1 IgG. The half-life of CYP2E1 was about 2.5 h, and the various substrates or ligands modified the turnover process within intact cells as described for the cycloheximide experiments. More than 20 different reagents including antioxidants, physiological metabolites, lysosomal inhibitors, and protease inhibitors were screened for possible effects on CYP2E1 proteolytic degradation. Dibutyryl cAMP had no effect on CYP2E1 activity or turnover. Among those reagents tested so far, the serine protease inhibitor 1-chloro-3-tosylamido-7-amino-2-heptanone hydrochloride exhibited some protection against CYP2E1 degradation. To demonstrate whether the proteasome complex is involved in this process, Czb-Ile-Glu(OtBu)-Ala-leucinal (PSI) as a cell penetrating aldehydic proteasome inhibitor and Czb-Leu-norleucinal (calpeptin inhibitor) as an aldehydic nonproteosomal protease inhibitor were used to examine their effect on both the normal and the CCl4-stimulated CYP2E1 proteolytic degradation pathways. Treatment with PSI at concentrations ranging from 5 to 80 microM resulted in a dose-dependent protection against the loss of both the normal CYP2E1 and the CCl4-modified CYP2E1. The maximum protection by PSI at a concentration of 80 microM after a 12-h chase period was about 60% in cells treated with 2 mM CCl4 or 75% in cells without CCl4 treatment. Calpeptin inhibitor afforded little or no protection against CYP2E1 degradation in the absence or presence of CCl4. PSI did not inhibit CYP2E1 catalytic activity, suggesting that it was not a ligand for CYP2E1. These results indicate that human CYP2E1 has a short half-life span and that substrates can significantly modify its turnover rate in intact HepG2 cells. The proteasome proteolytic pathway may be involved in the degradation process of both the normal and the CCl4-modified human CYP2E1 in this model.


Covert processing of words and pictures in nonsemantic variants of primary progressive aphasia.
The inability to name objects (anomia) is one of the most common findings in the neurologic examination of primary progressive aphasia (PPA). In the semantic variant of PPA, the anomia is profound and reflects a combination of object naming and word comprehension deficits. In contrast, nonsemantic variants of PPA display a more selective impairment of object naming, without corresponding impairments of word comprehension. The aim of the present study was to explore the nature of the anomia in nonsemantic variants of PPA with a sensitive chronometric test of covert word/picture association. We tested priming effects in 12 patients with nonsemantic variant of PPA and 18 controls. Stimuli consisted of written words and line pictures of concrete objects. Within-format (word-word and picture-picture) and cross-format (word-picture and picture-word) priming effects were assessed by measuring the shortening of response times to the second versus initial presentation of corresponding stimulus pairs. In addition to the expected impairment of picture-to-word priming, a condition simulating object naming, the nonsemantic PPA patients also showed unexpected impairments of word-to-picture and word-to-word priming. Picture-to-picture priming was preserved, demonstrating the selectivity of the deficit for lexical processing. These findings show that the information processing bottleneck in patients with nonsemantic variants of PPA is not confined to the stage of lexical access but that it also extends into the prior levels of lexical semantics. The boundaries between the semantic and nonsemantic variants are therefore far from rigid.


Neuronal regeneration: extending axons from bench to brain.
Many studies have shown that myelin in the central nervous system strongly inhibits the regeneration of axons, so it comes as a surprise to discover that adult neurons transplanted into the brain rapidly extend their axons through myelinated pathways.


Sports Medicine: Exertional Heat Illness.
Exertional heat illness (EHI), specifically exertional heat stroke (EHS), is one of the three leading causes of death in young athletes. In the United States, the incidence of EHI appears to be increasing. The human body has multiple mechanisms to dissipate heat, including conduction, convection, radiation, and evaporation via perspiration. Limitations on heat dissipation occur in hot and humid weather and are increased during intense exercise. Dehydration further decreases ability to tolerate heat, and these factors increase the risk of EHI. EHI is a spectrum of conditions based on severity. The severity of a heat illness may not be apparent initially. Morbidity and mortality are related directly to the duration of body temperature elevation. Effective management requires rapid cooling of the body, optimally with cold water immersion of the patient, initiated as soon as possible. After cooling has achieved a reasonable temperature (ie, approximately 39°C [102.2°F]), the patient should be transported to the closest emergency department. Subsequent management depends on recovery time and potential late complications, including rhabdomyolysis and organ damage. After an EHI, athletes should not perform significant physical activity for at least 7 days. Prevention is based on acclimatization and maintenance of adequate hydration.


Working Against the Clock: A Model for Rural STEMI Triage.
Residents in rural communities have a higher incidence of cardiac death and risk factors associated with cardiac disease. Living in a rural region can add precious time that amplifies cardiac death during an ST-elevated myocardial infarction (STEMI) episode. The consensus is that improved efficiencies can increase myocardial salvage and decrease STEMI mortality rates. This article identifies issues that may impact pre-hospital STEMI triage of patients in a rural region of the United States (U.S.). A qualitative research design was chosen to gain insight into emergency personnel perceptions of pre-hospital STEMI triage. The participants (n = 18) were obtained from a convenience sample in rural Northeast Texas, U.S. Data were gathered by individual and group semi-structured interviews. Themes were identified, synthesized, and oriented to offer a basis for understanding opportunities to improve the delivery of rural STEMI care. This study demonstrated that quality improvement initiatives aimed at achieving pre-hospital STEMI triage efficiencies have dependencies on teamwork, technology, and training in the context of 3 stages (a) pre-transport, (b) door-to-door, and (c) post-transport. A pre-hospital STEMI triage model is offered based on the findings. By incorporating this model, emergency medical coordinators in rural communities have a better opportunity to facilitate timely reperfusion therapy for this high-risk population.


"It's fundamental to the work that we do": Genetic counselors' perceptions of their role in clients' mental well-being.
The role of a genetic counselor is to assist individuals and their families to comprehend and adapt to genetic information. However, a genetic counselor's role in clients' mental well-being is unclear. Mental well-being is an important component of overall health and it can be affected during the adaptation to genetic information. It is, therefore, essential to consider how mental well-being is viewed in genetic counseling practice. Our research aimed to investigate genetic counselors' perceptions of their role in clients' mental well-being. Our objectives were to (1) understand what genetic counselors perceived their role to be in clients' mental well-being and (2) investigate what factors influence genetic counselors' perceptions of practice. We recruited participants via advertisements in the Human Genetics Society of Australasia and the Australasian Society of Genetic Counselors newsletters, and through the Genetic Support Network of Victoria social media. We completed semi-structured in-depth interviews with 12 Australian genetic counselors and analyzed the interviews using inductive thematic analysis. We found that genetic counselors viewed clients' mental well-being as an important and crucial part of their practice. Three key themes were identified, first, all the participants' views of clients' mental well-being were shaped by personal and professional beliefs. Second, all participants noted that there were factors external to them, such as workplace and professional guidelines, which shaped their role in clients' mental well-being. Third, all those interviewed noted the boundaries of their professional role in clients' mental well-being. From these three themes, we determined that genetic counselors see clients' mental well-being as an integral part of their practice. Our findings add to the extant literature and can shape future practice in this field. Furthermore, we identified how future research priorities could further our knowledge in this area.


Controlled Decomposable Hydrogel Triggered with a Specific Enzyme.
In this study, superabsorbent polyelectrolyte hydrogels were synthesized by cross-linking a nondegradable poly (allylamine hydrochloride) (PAH) and a recombinant protein with a specific enzymatic cleavage site. The recombinant protein was produced by E. coli with the pET-32b(+) plasmid, which is featured with the thioredoxin (Trx) gene containing a thrombin recognition site and a T7/lac hybrid promoter for high expression of recombinant protein. The swelling test shows that the composite hydrogel still maintained a high swelling ratio to 900% when 15% recombinant protein was cross-linked with PAH. The degradation test shows that such a PAH composite hydrogel could be decomposed by the addition of specific enzyme thrombin, which might lead to new biomedical applications of hydrogels needed to be decomposable by specific time not determined by the time period.


Amplification and analysis of Miocene plant fossil DNA.
Ancient DNA has been extracted and sequenced from several animal and plant specimens. Previous considerations of the damage to ancient DNA have suggested that both the age and size of DNA fragments that can be retrieved and sequenced may be limited, the former to between several thousand and at most tens of thousands of years old, and the latter to at most a few hundred bases. A recent report of a 770 base pair (b.p.) sequence from the chloroplast gene rbcL from a Miocene Magnolia latahensis leaf indicates that both estimated limitations may be too conservative. Further work has indicated that analysis of Miocene fossil DNA can be replicated, and can, therefore, open up the prospects for future development of the field of molecular palaeontology. Successful amplification of fossil DNA is sometimes confounded by factors inherent to fossil DNA or to samples with minimal amounts of target DNA. Techniques that alter denaturation, reduce inhibitors and the problem of contaminants, and repair DNA prior to polymerase chain reaction amplification can increase the probability of success.


Speech perception enhanced by noise in listeners with normal hearing.
Most often, noise is considered a major factor in the degradation of listening conditions. Recently, however, there is increasing evidence suggesting that the addition of low-intensity noise can improve signal detection in non-linear systems. While this phenomenon has been described in physical systems, very little has been documented regarding its functional significance in the human sensory system in general, and in the auditory system in particular. The purpose of the present study was to investigate the benefit of adding noise to the recognition of speech already embedded in background noise. Participants included 27 adults with normal hearing, between 20 and 30 years of age. Speech stimuli were consonant-vowel-consonant monosyllabic words. Babble noise (BN) was added until word recognition dropped to threshold levels (below 50%). Additional low-level noise (LLN) was added to the words + BN in an alternating design (i.e., words + BN + LLN, words + BN, etc.). For each participant, word recognition scores were based on 25 words in BN and 25 words in BN + LLN. The number of words was distributed unequally across the conditions. The results show that for 63% of the participants, adding LLN enhanced scores significantly by 4-32%. Of these participants, 70% showed that adding LLN to speech-in-noise improved performance by more than 12%. Additional noise seems to help when word recognition score in BN was lower than 50%. These results provide first-time evidence for the benefit of low-intensity noise in order to enhance speech-in-noise in hearing listeners.


Inverse Association Between Atopy and Melanoma: A Case-control Study.
Heightened cutaneous immune surveillance in atopic patients may inhibit development of melanoma. The aim of this study was to analyse the association between atopy and melanoma (development and outcome). A total of 188 cases of melanoma and 596 healthy controls were interviewed by telephone with a standardized questionnaire on atopic, demographic and melanoma characteristics. Cases were matched with controls on important confounders (age, sex, sunburn sensitivity, hair colour, number of moles, sunburn as juvenile, ever solarium, familial melanoma). Melanoma outcome data (disease relapse and death) within cases were retrieved. Analysis showed a general inverse association between atopy and melanoma development, but this was statistically significant only for a history of personal atopy (odds ratio 0.53, 95% confidence interval: 0.30-0.96, p-value = 0.04). Among melanoma patients, atopy did not affect survival or progression. In conclusion, this study suggests an inverse association between a history of atopy and melanoma development, but not with disease progression.


Reduction of insulin-stimulated glucose uptake by peroxynitrite is concurrent with tyrosine nitration of insulin receptor substrate-1.
Inducible nitric oxide synthetase plays an essential role in insulin resistance induced by a high-fat diet. The reaction of nitric oxide with superoxide leads to the formation of peroxynitrite (ONOO-), which can modify several proteins. In this study, we investigated whether peroxynitrite impairs insulin-signalling pathway. Our experiments showed that 3-(4-morpholinyl)sydnonimine hydrochloride (SIN-1), a constitutive producer of peroxynitrite, dose-dependently inhibited insulin-stimulated glucose uptake. While SIN-1 did not affect the insulin receptor protein level and tyrosine phosphorylation, it reduced the insulin receptor substrate-1 (IRS-1) protein level, and IRS-1 associated phosphatidylinositol-3 kinase (PI-3 kinase) activity. Although SIN-1 did not induce Ser307 phosphorylation of IRS-1, tyrosine nitration of IRS-1 was detected in SIN-1-treated-Rat1 fibroblasts expressing human insulin receptors. Mass spectrometry showed that peroxynitrite induced at least four nitrated tyrosine residues in rat IRS-1, including Tyr939, which is critical for association of IRS-1 with the p85 subunit of PI-3 kinase. Our results suggest that peroxynitrite reduces the IRS-1 protein level and decreases phosphorylation of IRS-1 concurrent with nitration of its tyrosine residues.


Sudden cessation of fluoxetine before alcohol drinking reinstatement alters microglial morphology and TLR4/inflammatory neuroadaptation in the rat brain.
Preclinical studies on the effects of abrupt cessation of selective serotonin reuptake inhibitors (SSRIs), a medication often prescribed in alcohol use disorder (AUD) patients with depression, results in alcohol consumption escalation after resuming drinking. However, a potential neuroinflammatory component on this escalation remains unexplored despite the immunomodulatory role of serotonin. Here, we utilized a rat model of 14-daily administration of the SSRI fluoxetine (10 mg/kg/day) along alcohol self-administration deprivation to study the effects of fluoxetine cessation on neuroinflammation after resuming alcohol drinking. Microglial morphology and inflammatory gene expression were analyzed in prelimbic cortex, striatum, basolateral amygdala and dorsal hippocampus. Results indicated that alcohol drinking reinstatement increased microglial IBA1 immunoreactivity and altered morphometric features of activated microglia (fractal dimension, lacunarity, density, roughness, and cell area, perimeter and circularity). Despite alcohol reinstatement, fluoxetine cessation modified microglial morphology in a brain region-specific manner, resulting in hyper-ramified (spatial complexity of branching), reactive (lower heterogeneity and circularity)-like microglia. We also found that microglial cell area correlated with changes in mRNA expression of chemokines (Cx3cl1/fractalkine, Cxcl12/SDF1α, Ccl2/MCP1), cytokines (IL1β, IL6, IL10) and the innate immune toll-like receptor 4 (TLR4) in dorsal hippocampus. Specifically, TLR4 correlated with microglial spatial complexity assessed by fractal dimension in striatum, suggesting a role in process branching. These findings suggest that alcohol drinking reinstatement after fluoxetine treatment cessation disturbs microglial morphology and reactive phenotype associated with a TLR4/inflammatory response to alcohol in a brain region-specific manner, facts that might contribute to alcohol-induced damage through the promotion of escalation of alcohol drinking behavior.


Transport of fibroblast growth factor 2 in the pericellular matrix is controlled by the spatial distribution of its binding sites in heparan sulfate.
The heparan sulfate (HS) chains of proteoglycans are a key regulatory component of the extracellular matrices of animal cells, including the pericellular matrix around the plasma membrane. In these matrices they regulate transport, gradient formation, and effector functions of over 400 proteins central to cell communication. HS from different matrices differs in its selectivity for its protein partners. However, there has been no direct test of how HS in the matrix regulates the transport of its partner proteins. We address this issue by single molecule imaging and tracking in fibroblast pericellular matrix of fibroblast growth factor 2 (FGF2), stoichiometrically labelled with small gold nanoparticles. Transmission electron microscopy and photothermal heterodyne imaging (PHI) show that the spatial distribution of the HS-binding sites for FGF2 in the pericellular matrix is heterogeneous over length scales ranging from 22 nm to several µm. Tracking of individual FGF2 by PHI in the pericellular matrix of living cells demonstrates that they undergo five distinct types of motion. They spend much of their time in confined motion (∼110 nm diameter), but they are not trapped and can escape by simple diffusion, which may be slow, fast, or directed. These substantial translocations (µm) cover distances far greater than the length of a single HS chain. Similar molecular motion persists in fixed cells, where the movement of membrane PGs is impeded. We conclude that FGF2 moves within the pericellular matrix by translocating from one HS-binding site to another. The binding sites on HS chains form non-random, heterogeneous networks. These promote FGF2 confinement or substantial translocation depending on their spatial organisation. We propose that this spatial organisation, coupled to the relative selectivity and the availability of HS-binding sites, determines the transport of FGF2 in matrices. Similar mechanisms are likely to underpin the movement of many other HS-binding effectors.


Sharps safety devices.
Injuries from needles or other sharps are a danger to patients and clinicians alike, particularly due to the risk of bloodborne pathogen transmission. One way to reduce the likelihood of such injuries is to implement protective devices as substitutes for more dangerous conventional products. Over the years, Health Devices has evaluated several sharps safety devices. In this issue, we evaluate four new types of protective alternatives: disposable prep razors, epidural needles, ophthalmic knives, and stitch cutters. Our Evaluation discusses whether these sharps safety devices deliver the added safety that they are designed to provide and whether they are effective at performing their intended clinical purposes.


Impact of Model for End-Stage Liver Disease allocation system on outcomes of deceased donor liver transplantation: A single-center experience.
From June of 2016, the Model for End-Stage Liver Disease (MELD)-based allocation system replaced the Child- Turcotte-Pugh (CTP) score-based system for organ allocation liver in Korea. The aim of this study was to analyze changes in outcomes and arising issues before and after the implementation of the MELD system. From June 2014 to June 2018, 129 patients were selected from recipients who underwent deceased donor liver transplantation (DDLT) in Seoul National University Hospital. Pediatric cases were excluded. According to the allocation system, patients were divided into two groups (52 in the MELD group and 77 in the CTP group). MELD scores of the two groups differed significantly (37.8 ± 2.0 in the MELD group vs. 31.0 ± 8.2 in the CTP group; p = 0.001). The etiology of patients was changed for liver transplantation. The proportion of alcoholic liver cirrhosis increased in the era of the MELD allocation system. However, proportions of hepatitis B related liver cirrhosis and hepatocellular carcinoma were decreased. Six-month mortality rate of the MELD group was 25.0%, which was higher than that (11.7%) of the CTP group (p = 0.022). The 90-day complication rate was significantly higher in the MELD group than in the CTP group (11.5% vs. 2.6%; p = 0.040). When the MELD allocation system was used to distribute livers to severely ill patients, it resulted in poorer outcomes after surgery and higher proportion of alcoholic cirrhosis. Thus, it is necessary to adjust the MELD allocation system so that outcomes after DDLT could be improved.


Cryotherapy as a treatment for psoriasis.
There are very few publications on the use of cryotherapy in the treatment of psoriasis. We performed an evaluation to determine its efficacy in small plaque psoriasis. We selected 63 patients who had a clinical diagnosis of chronic plaque-type psoriasis and and for each patient we evaluated two psoriatic plaques of almost the same size and severity on similar areas of the body. One plaque was sprayed with liquid nitrogen every other day for two weeks and the other plaque was untreated as a control. Complete resolution of the plaque occurred in four patients (6.35 %), mild to moderate resolution was evident in 19 cases (30.1 %), and no improvement occurred in 40 patients (63.5 %). Only one complication, superimposed infection, occurred. Cryotherapy may mediates mild resolution of plaques by inducing normal re-epithelization following the physical destruction of the lesions via a reverse Koebner phenomenon. Our findings suggest that cryotherapy is safe to use in the treatment of small-plaque psoriasis but that its efficacy is limited.


Combination of novel systemic agents and radiotherapy for solid tumors - part I: An AIRO (Italian association of radiotherapy and clinical oncology) overview focused on treatment efficacy.
Over the past century, technologic advances have promoted the evolution of radiation therapy into a precise treatment modality allowing for the maximal administration of dose to tumors while sparing normal tissues. In parallel with this technological maturation, the rapid expansion in understanding the basic biology and heterogeneity of cancer has led to the development of several compounds that target specific pathways. Many of them are in advanced steps of clinical development for combination treatments with radiotherapy, and can be incorporated into radiation oncology practice for a personalized approach to maximize the therapeutic gain. This review describes the rationale for combining novel agents with radiation, and provides an overview of the current landscape focused on treatment efficacy.


Xenotransplantation of human umbilical cord blood mononuclear cells to rats with D-galactosamine-induced hepatitis.
Cord blood is an attractive cell source in regenerative medicine and represents an alternative to bone marrow. The aim of this study was to investigate whether human umbilical cord blood mononuclear (HUCBM) cells might be valuable in hepatic regenerative medicine. HUCBM cells differentiated in vitro into hepatocytes, as suggested by expression of albumin, cytokeratin-18, glutamine synthetase, alpha-fetoprotein, and cytochrome P450 3A4 at both mRNA and protein levels in a time-dependent fashion. In contrast, the hematopoietic phenotype was gradually lost, as demonstrated by disappearance of CD45 expression. The regenerative potential of HUCBM cells was tested by using a human-to-rat xenotransplant model in which HUCBM cells were intraportally injected into rats with D-galactosamine-induced hepatitis. Liver histology and biochemical markers of hepatic damage were determined. Presence of human cells was detected in blood and liver of both control and D-galactosamine-treated animals. Cell transplantation produced an improvement in both the histological damage and liver function, as demonstrated by plasma values of alkaline phosphatase, gamma-glutamyl transferase, lactate dehydrogenase, and total and direct bilirubins. Results obtained suggest that HUCBM cells are capable of hepatic engraftment in this human-to-rat xenotransplant model and that transplantation of HUCBM cells may be a suitable therapy for liver disease.


Community violence: its impact on the development of children and implications for nursing practice.
An alarming increase in the prevalence of violent crime in the United States has lead to the birth of a new subset of victims, children who witness acts of violence. Results of multiple studies suggest that chronic exposure to violence has a profound negative impact on children's cognitive, social, psychologic, and moral development. As primary care providers, pediatric nurses and nurse practitioners are well-positioned to assess these children for early signs of exposure to violence, offer guidance and counseling, and make referrals for proper treatment.


Higher sirt1 is associated with a better body composition in master sprinters and untrained peers.
Sirt1 is an enzyme involved in several anti-aging pathways. Associations between Sirt1, age, and body fat (BF) were assessed in master sprinters (MS; n = 35; 50.25 ±5.93 yr.), untrained young non-athletes (UY; n = 32; 23.78 ±3.98 yr.), and untrained middle-aged (UMA; n = 24; 47.29 ±8.04 yr.). BF was assessed using a skinfold protocol, and Sirt1 was measured in plasma by using commercial kits. Sirt1 of MS (17.18 ±4.77 ng/mL) was higher than UMA (6.36 ±2.29 ng/mL; p<0.0001) and did not differ from UY (20.26 ±6.20 ng/mL). Relative BF of MS was lower than UMA (12.71 ±4.07% vs. 22.13 ±4.18%; p<0.0001). Sirt1 was negatively correlated with chronological age (r = -0.735; p<0.0001) when combining UY and UMA in the analysis. However, when Sirt1 of MS and UY was analyzed together, no significant relationship between Sirt1 and chronological age was observed (r = -0.243; p = 0.083). Sirt1 correlated inversely with BF (r = -0.743; p<0.0001) for UY and UMA. Stepwise multiple regression revealed that being either a young or master athlete and body adiposity are possible predictors of Sirt1 levels. MS and UY were associated with higher levels of Sirt1, while UMA and increased BF were associated with lower levels of this enzyme. The relationships among Sirt1, BF, and chronological age of young and middle-aged non-athletes were not statistically significant when the middle-aged participants were MS. These findings suggest possible links between Sirt1 and body composition, which may play roles in the rate of biological aging.HighlightsLower levels of Sirt1 are associated with higher body fat.Master athlete lifestyle seems to promote higher Sirt1 Levels.


Biological coating of paper using silver nanoparticles.
The capacity of Ag nanoparticles to destroy various micro-organisms makes it one of the most powerful antimicrobial agents, an attractive feature against antibiotic resistant bacteria. Here, a simple method to develop coating of colloidal silver on paper using a biological method is presented. The coated paper was studied by scanning electron microscopy, X-ray diffraction technique and atomic absorption spectroscopy. The antibacterial activity of the coated paper against Escherichia coli and Staphylococcus aureus was measured by agar diffusion method. This study shows the potential use of the coated paper as a food antimicrobial packing material for longer shelf life.